Ex Parte Singh et al

Patent Trials and Appeals Board

Oct 29, 2014

12175441 - (D) (P.T.A.B. Oct. 29, 2014)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte RAJINDER SINGH, HUI LI, HAORAN ZHAO,
DONALD PAYAN, RAO KOLLURI, KIN TSO,
JOHN RAMPHAL, and SHIHAI GU
____________

Appeal 2012-004966
Application 12/175,441
Technology Center 1600
____________

Before DEMETRA J. MILLS, ULRIKE W. JENKS, and
CHRISTOPHER G. PAULRAJ, Administrative Patent Judges.

JENKS, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal1 under 35 U.S.C. § 134 involving claims directed to
2,4-pyrimidinediamine compounds that are useful for the modulation of
protein kinase C. The Examiner has rejected the claims as obvious. We
have jurisdiction under 35 U.S.C. § 6(b). We reverse.
STATEMENT OF THE CASE
“Protein kinases constitute a large family of structurally related
enzymes that are responsible for the control of a variety of signal

1 Appellants identify Rigel Pharmaceuticals, Inc. as the Real Party in
Interest. (App. Br. 3.)
App
App

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fall w

2 Sin
eal 2012-0
lication 12
duction pr
lved in “ce
tosis. . . .
lation of im
t 2: ¶ 5).
itions in w
n as PKC
Claims 1
d in the Cl
1 is repr
llows:
1. A com
N-oxide
The Exa
r 35 U.S.C
As Appe
sis on cla
ith that c

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04966
/175,441
ocesses w
ll prolifer
PKC-theta
mune res
The Speci
hich modu
) is therap
, 2, 4, 9–1
aims App
esentative
pound of
, or therap
miner has
. § 103(a)
llants do n
im 1, and
laim (App

S 2005/0
ithin cells”
ation, diffe
is primar
ponses an
fication di
lation or
eutically u
7, 20, 43,
endix of th
of the clai
formula I
eutically a
rejected cl
as unpate
ot argue t
claims 1, 2
. Br. 12).

234049 Al
2
(Spec. 1:
rentiation
ily implica
d in insulin
sclosed co
inhibition
seful” (id.
45, 47, an
e Appeal B
ms on app
:
cceptable
aims 1, 2,
ntable ove
he claims
, 4, 9–17,
37 C.F.R.
, published
¶ 3.) Prot
, metaboli
ted in T c
resistanc
mpounds f
of Protein
at 1: ¶ 2).
d 48 are on
rief (App
eal, and re
salt thereo
4, 9–17, 2
r Singh.2
separately
20, 43, 45
§ 41.37 (c
Oct. 20,
ein kinase
sm, and
ell activati
e in skelet
or “the tre
Kinase C

appeal, a
. Br. 24–3
ads in rele
f; wherein
0, 43, 45,
, we focus
, 47, and 4
)(1).
2005.
C’s are
on and
al muscle”
atment of
(also
nd can be
3).
vant part

: . . . .
47, and 48
our
8 stand or

App
App

The I
indiv
exem
gene
Man
comp
deve
Exam
claim
Find

any o

the c
meth
pyrim
eal 2012-0
lication 12
ssue
The Exa
idual com
plify a cla
ral formul
y of the co
ounds, an
lopment”
Does the
iner’s po
1?

ings of Fa
FF1. Th
f the insta
FF2. Th
laimed co
The Figu
ylpiperazi
idinediam
04966
/175,441
miner reco
ponents o
imed com
a and guid
mpounds
y one of w
(id. at 6).
preponde
sition that
ct
e Examin
ntly claim
e Examin
mpound:
re above,
no)phenyl
ine. (An
gnizes tha
f the claim
pound, [bu
ance to ma
discussed
hich coul
rance of th
Singh rend
er acknow
ed compo
er finds th
shows the
]-N4-(1,2,
s. 5.) “Thi
3
t although
ed molecu
t instead
ke the ins
above are
d be used a
e evidenc
ers obvio
ledges tha
unds” (An
at Singh d
positional
2,6,6-pent
s is a posi
Singh “di
le” (Ans.
finds] this
tantly clai
effective a
s a lead c
e of record
us the com
t Singh do
s. 5).
isclosed a
isomer 5-
amethylpi
tional isom
sclose[d] t
5), Singh “
art provid
med comp
nti-inflam
ompound
support t
position a
es not “ex
positional

fluoro-N2
peridin-4-y
er of the
he
do[es] not
es a
ounds.
matory
for further
he
s recited in
emplify
isomer of
-[3-(4-
l)-2,4-
claimed

Appeal 2012-004966
Application 12/175,441

4
compounds (i.e. the methyl substituent on the piperazinyl moiety cannot be
at the 4-position according to Claim 1).” (Id.)

Principle of Law
To establish obviousness, the Examiner must identify some reason
that would have led a chemist to modify a known compound. Takeda Chem.
Indus., Ltd. v. Alphapharm Pty., Ltd., 492 F.3d 1350, 1357 (Fed. Cir. 2007).
Generally, an obviousness inquiry concerning such “known compounds”
focuses on the identity of a “lead compound.” Eisai Co. Ltd. v. Dr. Reddy’s
Labs., Ltd., 533 F.3d 1353, 1359 (Fed. Cir. 2008).

Analysis
The Examiner arrives at the selection of compound No. 1219 in Singh
as the base compound for making modifications based on the structural
similarity to the claimed compound, recognizing that compound No. 1219
“is a positional isomer of the claimed compounds” (Ans. 5; FF 1–2), citing
In re Dillon, 919 F.2d 688 (Fed. Cir. 1990) in support (Ans. 9). The
Examiner explains that once structural similarity is established, it is not
necessary for the art to show the same or similar utility as claimed (id.).
“Motivation to modify the exemplified compounds in Singh, et al., would be
to develop compounds that possess superior pharmacokinetic or
pharmacodynamic properties.” (Ans. 6; see also Ans. 9.)
Appellants contend that the Examiner has not identified a reason to
select a particular compound from Singh as a lead compound (App. Br. 13).
Appellants explain that

Appeal 2012-004966
Application 12/175,441

5
Compound 1219 was tested in LD Tryptase assay, CHMC, IgE,
3 point. As shown on page 122 of Singh, the IC50 of Compound
1219 is more than 10 μM, with no measurable activity at 10 μM
concentration. In contrast, Singh's Compound 994 had an IC50
of 47 nanomolar in the LD Tryptase assay, i.e., greater than
200-fold more potent than Compound 1219.
(App. Br. 14.)
Given the present facts, we find that Appellants have the better
position. Whether a lead compound and a claimed compound have a
sufficiently close relationship frequently turns on their “structural
similarities and differences.” Daiichi Sankyo Co. v. Matrix Labs., Ltd., 619
F.3d 1346, 1352 (Fed. Cir. 2010). We agree with the Examiner that
compound 1219 is structurally close to the claimed compounds. Structural
similarity alone may be sufficient to establish a motivation to make
modifications in some instances. However, “[p]roperties must be considered
in the overall evaluation of obviousness, and the lack of any disclosure of
useful properties for a prior art compound may indicate a lack of motivation
to make related compounds.” In re Dillon, 919 F.2d at 698. Here, Singh
evaluated the properties of the disclosed compounds and concluded based on
their experimental parameters that compound No. 1219 did not display any
favorable activities (see Singh 44: ¶¶ 394-397, ¶ 399 compound # 1219).
To be sure, the present claims do not recite a particular property
associated with the compound, i.e., that they are protein kinase C
modulators. Thus, any positive activity associated with compound No. 1219
could provide a reasonable motivation to modify and make related
compounds. But in this case, the experimental results using a cultured
human mast cell-tryptase assay only showed a negative result for compound
No. 1219 (see Singh 44: ¶¶ 394-397, ¶ 399 compound # 1219; see also App.
Appeal 2012-004966
Application 12/175,441

6
Br. 14). The Examiner would like us to ignore these results, asserting that
the
[A]rt does not teach that these compounds are not anti-
inflammatory agents; rather, it indicates that these compounds
do not meet the threshold in an in vitro assay to warrant a “+”.
The art worker has no way of knowing how close these
compounds are to a “+” and, therefore, the data in Singh, et al.,
are not a negative teaching to direct the art worker away from
these compounds.
(Ans. 9–10.) We do not agree with the Examiner’s position that we can
simply disregard the unfavorable experimental data shown in the prior art.
A lead compound needs to be “a natural choice for further development
efforts.” Altana Pharma AG v. Teva Pharms. USA, Inc., 566 F.3d 999, 1008
(Fed. Cir. 2009). Here, the experimental results indicate that compound
No. 1219 is not an attractive candidate for further modification to improve
the activities for the purpose tested in Singh.
We recognize, but are not persuaded by, the Examiner’s position that
Singh provides the core structure and the individual building blocks, and
thereby render the claims obvious. Specifically, the Examiner explains
By way of analogy, if the instantly claimed compound is
represented by the formula A-Core-l, the prior art contemplates
subgroups A (among others) and 1 (among others) to be
attached to the Core. This art, then, exemplifies compounds A-
Core-2 and B-Core-l, thus providing guidance for the artisan to
attach A and 1 to the Core. Singh, et al., provides guidance
regarding how to make the instantly claimed compounds since
the art worker would merely be starting with different
beginning moieties already, taught by the art, to link to the
disclosed core.
(Ans. 8.)
Appeal 2012-004966
Application 12/175,441

7
Although we agree with the Examiner that the individual building
blocks are disclosed in Singh, we find that the Examiner has not provided a
sufficient rationale to pick compound No. 1219 as the starting point for
making modifications. Here, given the experimental data disclosed in Singh,
compound No. 1219 is not a “natural choice” for selection to improve upon
the compound’s inhibition of SYK kinase. See Altana Pharma AG, 566
F.3d at 1008. The Examiner provides no other persuasive reason to modify
the compound with the disclosed building blocks or to otherwise modify the
compound by changing the methyl position. Furthermore, we note that “‘[i]t
is impermissible within the framework of section 103 to pick and choose
from any one reference only so much of it as will support a given position,
to the exclusion of other parts necessary to the full appreciation of what such
reference fairly suggests to one of ordinary skill in the art.’” In re Hedges,
783 F.2d 1038, 1041 (Fed. Cir. 1986) (quoting In re Wesslau, 353 F.2d 238,
241 (CCPA 1965)).
For the reasons discussed above, we agree with Appellants’ position.
The Examiner has not persuasively shown that that there would have been a
reason to choose compound No. 1219 as the starting point for making
modifications to arrive at the presently claimed structure. We find that the
preponderance of the evidence does not support the Examiner’s position and
therefore reverse the rejection on appeal.
SUMMARY
We reverse the rejection of claims 1, 2, 4, 9–17, 20, 43, 45, 47, and 48
under 35 U.S.C. § 103(a) over Singh.

REVERSED
Appeal 2012-004966
Application 12/175,441

8

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